Nonspecific immunity and head and neck cancer: Blastogenesis reviewed and revisited Daniel P. Eskinazi, D.D.S., Ph.D.,* Joseph Helman, D.M.D.,** Abby G. Ershow, Sc.D., *** John J. Perna, D.D.S.. and Radu Mihail, M.D..**** Bethesda, Md., and Washington, D.C. NATIONAL INSTITUTE OF DENTAL RESEARCH AND WALTER REED ARMY MEDICAL CkNTER The present study suggests a correlation between concanavalin A-driven blastogenesis and the clinical course of head and neck cancer. Blastogenesis assays were conducted on peripheral blood lymphocytes from controls and from patients with squamous cell carcinoma (SCC) of the head and neck. Our results indicated that 3H-thymidine incorporation in response to concanavalin A and phytohemagglutinin stimulation were significantly lower for patients’ than for controls’ lymphocytes, whereas PWM stimulation was not statistically different in these two groups. Differences between patients and controls were most notable with concanavalin A stimulation. Five of seventeen patients had a response to concanavalin A stimulation that was in the normal range when expressed as relative to control values. The clinical course of these five patients seems to point to a better prognosis than that of the remaining patients who had below-normal mitogenic responses. (ORAL SURG. ORAL MED. ORAL PATHOL. 60~642-647, 1985) A s originally formulated by Burnet,‘*2 the theory of immune surveillance postulates that the normal function of the immune system is to recognize and destroy tumor cells. Enthusiastically accepted at first, this concept was later questioned:s4 but it is now attracting a renewed interest after the recent discovery of natural killer immunity.5 That the immune system is involved in tumor control is now accepted, but it need not be an all-or-none phenom- enon. The mechanism of immune surveillance is not known, but it probably requires an intact immune system. Experimentally, evaluation of the integrity of the immune system relies on a battery of tests, among which blastogenesis is one of the simplest and oldest. In blastogenesis experiments, lymphocytes iso- lated from the peripheral blood (PBL) are stimulat- *Laboratory of Oral Medicine, National Institute of Dental Research, National Institutes of Health, Bethesda, Md. **Clinical investigations and Patient Care Branch, National Institute of Dental Research. ***Biostatistics Branch, National Cancer institute, National Institutes of Health. ****Department of Otolaryngology/Head and Neck Surgery, Walter Reed Army Medical Center, Washington, D.C. ed with substances called mitogens, which induce the PBL to divide and therefore synthesize DNA. The introduction of a DNA-specific radiolabeled nucleo- tide (3H-TdR) into the culture medium at an optimal time results in the synthesis of radiolabeled DNA. The cells are then lysed, their DNA is collected on special filters, and the filter-bound radioactivity is counted. This provides a means by which to estimate the amount of DNA synthesized and, therefore, to evaluate the mitotic activity of the cells. Mitogens used to induce PBL proliferation are often cell subset-specific. Thus, concanavalin A (Con A) and phytohemagglutinin (PHA) generate mostly T-cell activity, whereas pokeweed mitogen (PWM) gener- ates T-dependent B-cell proliferation.7 Blastogenesis studies on the PBL of patients with oral cancer have revealed reproducible trends, but they have also shown discrepancies. Several labora- tories have found that blastogenic activity is lower for the PBL of patients than for that of controls. This applies mostly to Con A- and PHA-driven blastogen- esis,*-” whereas PWM-driven blastogenesis has been found to be similar in both patient and control groups.lO*” This observation is of interest, as PWM stimulation should be performed in parallel with Con 642